Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms

Abstract:

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition.

Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC.

Design, setting, and participants: This case-control study conducted at a tertiary care psychiatric hospital in Canada from April 1, 2021, to June 30, 2022, compared TSPO VT of specific brain regions in 20 participants with COVID-DC with that in 20 healthy controls. The TSPO VT was measured with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) PET.

Main outcomes and measures: The TSPO VT was measured in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus. Symptoms were measured with neuropsychological and psychological tests, prioritizing outcomes related to striatal function.

Results: The study population included 40 participants (mean [SD] age, 32.9 [12.3] years). The TSPO VT across the regions of interest was greater in persons with COVID-DC (mean [SD] age, 32.7 [11.4] years; 12 [60%] women) compared with healthy control participants (mean [SD] age, 33.3 [13.9] years; 11 [55%] women): mean (SD) difference, 1.51 (4.47); 95% CI, 0.04-2.98; 1.51 divided by 9.20 (17%). The difference was most prominent in the ventral striatum (mean [SD] difference, 1.97 [4.88]; 95% CI, 0.36-3.58; 1.97 divided by 8.87 [22%]) and dorsal putamen (mean difference, 1.70 [4.25]; 95% CI, 0.34-3.06; 1.70 divided by 8.37 [20%]). Motor speed on the finger-tapping test negatively correlated with dorsal putamen TSPO VT (r, -0.53; 95% CI, -0.79 to -0.09), and the 10 persons with the slowest speed among those with COVID-DC had higher dorsal putamen TSPO VT than healthy persons by 2.3 (2.30 divided by 8.37 [27%]; SD, 2.46; 95% CI, 0.92-3.68).

Conclusions and relevance: In this case-control study, TSPO VT was higher in patients with COVID-DC. Greater TSPO VT is evidence for an inflammatory change of elevated gliosis in the brain of an individual with COVID-DC. Gliosis may be consequent to inflammation, injury, or both, particularly in the ventral striatum and dorsal putamen, which may explain some persistent depressive and cognitive symptoms, including slowed motor speed, low motivation or energy, and anhedonia, after initially mild to moderate COVID-19 illness.

Source: Braga J, Lepra M, Kish SJ, Rusjan PM, Nasser Z, Verhoeff N, Vasdev N, Bagby M, Boileau I, Husain MI, Kolla N, Garcia A, Chao T, Mizrahi R, Faiz K, Vieira EL, Meyer JH. Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms. JAMA Psychiatry. 2023 May 31:e231321. doi: 10.1001/jamapsychiatry.2023.1321. Epub ahead of print. PMID: 37256580; PMCID: PMC10233457. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233457/ (Full text)

Exploring anhedonia in adolescents with Chronic Fatigue Syndrome (CFS): A mixed-methods study

Abstract:

Background: Chronic Fatigue Syndrome (CFS/ME) may get in the way of enjoying activities. A substantial minority of adolescents with CFS/ME are depressed. Anhedonia is a core symptom of depression. Anhedonia in adolescents with CFS/ME has not been previously investigated.

Method: One hundred and sixty-four adolescents, age 12 to 18, with CFS/ME completed a diagnostic interview (K-SADS) and questionnaires (HADS, RCADS). We used a mixed-methods approach to explore the experience of anhedonia and examine how common it is, comparing those with clinically significant anhedonia to those without.

Results: Forty-two percent of adolescents with CFS/ME reported subclinical or clinical levels of anhedonia. Fifteen percent had clinically significant anhedonia. Thematic analysis generated two themes: (1) stopping activities that they previously enjoyed and (2) CFS/ME obstructs enjoyment. Most (72%) of those who reported clinically significant anhedonia met the depression diagnostic criteria. Those who were depressed used more negative language to describe their experience of activities than in those who were not depressed, although the themes were broadly similar.

Conclusions: Experiencing pleasure from activities may be affected in CFS/ME, particularly in those who are depressed. Anhedonia may get in the way of behavioural strategies used within CFS/ME treatments.

Source: Smith L, Crawley E, Riley M, McManus M, Loades ME. Exploring anhedonia in adolescents with Chronic Fatigue Syndrome (CFS): A mixed-methods study. Clin Child Psychol Psychiatry. 2021 Apr 16:13591045211005515. doi: 10.1177/13591045211005515. Epub ahead of print. PMID: 33863235. https://pubmed.ncbi.nlm.nih.gov/33863235/

Characterization of fatigue states in medicine and psychiatry by structured interview

Abstract:

CONTEXT: Unexplained fatigue states are prevalent, with uncertain diagnostic boundaries.

OBJECTIVE: Patients with fatigue-related illnesses were investigated by questionnaire and a novel semistructured interview to identify discriminatory features.

METHODS: Cross-sectional samples of women from specialist practices with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or major depression (n = 16) were recruited. Additionally, two longitudinal samples were studied: women with fatigue associated with acute infection who subsequently developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n = 21), and women undergoing adjuvant therapy for breast cancer experiencing treatment-related fatigue who subsequently developed PCF (n = 16) or recovered uneventfully (n = 16). Patients completed self-report questionnaires, and trained interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The receiver operating characteristics curves of the interview were measured against clinician-designated diagnoses. Cluster analyses were performed to empirically partition participants by symptom characteristics.

RESULTS: The interview had good internal consistency (Cronbach alpha “fatigue” = .83), and diagnostic sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major depression (100% and 72%), with reasonable parameters for PCF (72% and 58%). Empirical clustering by “fatigue” or “neurocognitive difficulties” items allocated most patients to one group, whereas “mood disturbance” items correctly classified patients with depression only.

CONCLUSIONS: The Semi-structured Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing fatigue-related conditions. The symptom domains of fatigue and neurocognitive difficulties are shared across medical and psychiatric boundaries, whereas symptoms of depression such as anhedonia are distinguishing.

 

Source: Bennett BK, Goldstein D, Chen M, Davenport TA, Vollmer-Conna U, Scott EM, Hickie IB, Lloyd AR. Characterization of fatigue states in medicine and psychiatry by structured interview. Psychosom Med. 2014 Jun;76(5):379-88. https://www.ncbi.nlm.nih.gov/pubmed/25076512